Not Applicable
Not Applicable
1. Field of the Invention
This invention pertains generally to aerosol generating devices, and more particularly to inhalers which may be used to dispense liquid medication in short bursts of aerosol.
2. Description of the Background Art
Some medicines cannot withstand the environment of the digestive tract and must be delivered to the bloodstream intravenously or by some other means. One effective means for delivery of such medications to the blood stream is through the membranes and air passageways of the lung.
Inhalers of various types have been widely used for inhalation delivery of aerosols containing medication or other constituents to the conductive airways of the lung and the gas exchange regions of the deep lung. Aerosols are relatively stable suspensions of finely divided droplets or solid particles in a gaseous medium. When inhaled, aerosol particles may be deposited by contact upon the various surfaces of the respiratory tract leading to the absorption of the particles through the membranes of the lung into the blood stream and providing the desirable therapeutic action, or planned diagnostic behavior depending on the particular properties of the particles.
Because of the high permeability of the membranes of the lung and the copious flow of blood through the lung, medications deposed in the lung can readily enter the blood stream for action throughout the body. This may also allow for lower initial doses than would be required to be taken orally to achieve the desired concentration of medication in the blood. Other medications can directly influence the airway epithelium and effect responses via various airway receptors.
Properly generated and formulated aerosols can therefore be helpful in medical treatment. Inhalable aerosol particles capable of deposition within the lung are those with an aerodynamic equivalent diameter between 1 and 5 micrometers.
Still other types of aerosol particles deposited in the lung can act as tracers of airflow or indicators of lung responses and otherwise be a valuable diagnostic tool.
An inhaler produces a burst of aerosol consisting of fine particles intended for inhalation by a patient with a single breath. Inhalers are popular aerosol delivery devices because they are generally portable and are convenient to use. The particle size of the aerosol emitted from a typical inhaler is required to be considerably smaller than a conventional spray atomizer to ensure the appropriate deposition within the lungs. Atomizers are typically equipped with reservoirs, nozzles, and bulbs. Upon squeezing the bulb, liquid medication, which is placed within the reservoir, is entrained and sprayed by the nozzle for inhalation by the patient. However, the particle size produced by atomizers is too large for effective deposition in the lungs, although variants of the technique are still used for deposition of topical medication into the nasal cavity and associated tissues. A further disadvantage of atomizers is that they are unable to deliver a consistent dose due to discrepancies in user technique and the duration of each burst. Accordingly, atomizers are appropriate for delivery of medication to the sinus cavity, where the larger aerosol particle size is more effective for deposition but inappropriate for deposition in the deep lung.
Inhalers known in the art employ several techniques to achieve effective aerosolization of medicines for deposition in the lung. Commonly, inhalers are pre-packaged containers containing a mixture of medication to be aerosolized and a low saturation pressure vapor or gas, such as chlorofluorocarbons (CFCs), which are used as a propellant. The canister carrying the mixture of medication and propellant is equipped with a valve. When the valve is actuated, the inhaler dispenses a set amount of liquid and medication through a jet orifice, creating a spray. Upon release into the atmosphere, the low saturation pressure propellant is able to evaporate quickly leaving small aerosol particles of medication that are suitable for immediate inhalation. One disadvantage to this approach is that the propellant and the medication must be mixed for a significant period of time prior to inhalation by the patient, making them unsuitable for many medications. Furthermore, the pre-mixing of the medication and the propellant requires a different approach to gain regulatory approval, necessitating significant development time and capital, thereby significantly increasing the ultimate cost to the patient than with liquid formulations of same medication. To prevent agglomeration of the medication within the canister, surfactants are also added to the formulation, which often leave an undesirable taste in the mouth of the patient after inhalation.
Another inhaler strategy increasingly being employed is the aerosolization of dry medicament powders. Medicinal powders are prepared in advance and placed in a reservoir within the inhaler, or within blister pouches. Blister pouches have the advantage of being able to better preserve the powder from contamination and moisture. When the patient is ready for a dose of medication, they either access the reservoir to dispense an appropriate amount of powdered medication, or puncture a blister pouch containing the powder medicament. Aerosolization is typically achieved by the gas flow produced by the inhalation of the patient. However, the aerosolization of medicinal powders is plagued by problems of moisture contamination and the inconsistencies in inhalation effort by the patient from dose to dose. Furthermore, powder formulations are as expensive to develop as pre-mixed propellants.
A third inhaler strategy employs ultrasonic energy to aerosolize bursts of liquid medication. These devices require precise electronic valves and associated electronic circuitry, making them expensive to manufacture and prone to malfunction. Additionally, the particle size of the aerosol produced by these devices is often too large for optimal deposition in the lung.
Therefore, a need exists for a technology which can deliver aerosol bursts of liquid medication at a particle size that is appropriate for lung deposition and which is inexpensive for the patient, produces consistent output, uses a formulation which is inexpensive to develop and produce, that is reliable, that is easy to use, and which does not require the mixing of medication and propellant until the moment of aerosolization. The present invention satisfies this need, as well as others and has the further advantages of providing superior aerosol quality, and being lightweight and portable.
The present invention generally pertains to a pneumatic inhaler that is able to deliver a controlled burst or dose of aerosol from a reservoir of liquid medication. The invention is appropriate for the aerosolization of liquid medication that is in solution or in suspension form. The invention is also ideal for the delivery of unique and specialty liquid medications in short aerosol bursts because no additional formulation development is needed. The apparatus has the further advantage of being able to deliver multiple medications, as mixed by the patient, doctor, or pharmacist, with a single burst of aerosol at a repeatable output. Because the medication and the propellant are not mixed until aerosolization occurs, the current invention is appropriate for more pharmaceutical agents than can be used by currently available inhalers at a substantial cost savings.
By way of example and not of limitation, a first embodiment of the present invention employs a cartridge or cylinder for containing virtually any type of compressed gas. Typically, carbon dioxide gas is used at a preferred pressure of approximately 750 psi, because the gas has a low critical temperature and pressure, allowing a small canister to carry significantly more than if filled with many other gases. The compressed gas is released in small bursts by a valve actuated by the patient, which delivers the gas to the supersonic shock nozzle. The nozzle comprises a jet orifice from which the compressed gas discharges into a sonic shock chamber. Provided that substantial backpressure is supplied, a supersonic jet exits from the jet orifice of the nozzle, which may be over expanded, under expanded or perfectly expanded. If the jet is over or under expanded, the supersonic jet, which remains at approximately the diameter of the jet orifice and which travels down the axis of the shock chamber, establishes a series of reflected compression and expansion shock waves. A perfectly expanded jet will have a cylindrical shock wave that envelops the entire jet. Although this would be preferable for the production of aerosol, it is impractical as a result of changes in supply pressure and the desired dimensional scale of the preferred embodiment of the current invention. Therefore, the nozzle is designed to be over expanded, and this is considered optimum.
Upon formation of the jet and the resulting reflected shock waves in the shock chamber, a vacuum is generated which causes liquid from the reservoir to be entrained through the liquid feed channels into the shock chamber. The preferred design channels the incoming fluid circumferentially around the shock chamber. Upon entrainment of the liquid into the shock chamber, the initially entrained liquid comes in contact with the shear forces created by the shock waves, producing copious amounts of aerosol particles suitable for inhalation. Shock waves are uniquely able to produce tremendous quantities of aerosol with good particle size for inhalation because they have the property of having large pressure differences over very small distances, thus making them able to generate substantial shear forces. The result of liquid traveling across this shock boundary is to be violently and physically disturbed, thus disintegrating into a dense burst of aerosol with appropriate particle size for inhalation. This represents a significant advance over traditional atomizers, which lacked the ability to produce shock waves of any design or magnitude, resulting in lower output and larger particle size.
Once the liquid has been entrained into the shock chamber and jet, the integrity of the jet and resulting reflecting shock waves is destroyed, resulting in a reduction in the subsequent production of aerosol particles than is produced in the initial burst. The subsequent production also has a generally larger particle size than the initial burst. The overall result is an initial burst of aerosol ideally suited for an inhaler, generally lasting less than a second. The output and particle size of such an inhaler is substantially better than would be predicted from the steady state operation of an atomizer or nebulizer nozzle of similar design. It is not possible to employ the same technique in the design and manufacture of an atomizer or nebulizer, because these devices are intended to run for durations of time longer than the first initial moments and the unique phenomena of the current invention only occurs at the moment of introduction of fluids to the reflected shock waves. Since the majority of aerosolization takes place in the first moment of liquid entrainment, little compressed gas is required for a burst of aerosol, making it possible, and efficient, to store enough carbon dioxide in a small canister for 200 bursts or more.
Although not of optimum design under most conditions, a similar result is obtained by having a shock region instead of a shock chamber. In such a design, the jet exits directly into a generally unenclosed region allowing the formation of reflected shock waves within the exiting jet. Liquid is entrained through one or more feed tubes placed proximally to the jet at a sufficient distance to generate a vacuum. Again, once the entrained liquid comes into contact with the reflected shock waves, a tremendous amount of aerosol particles are produced, and the integrity of the sonic jet and the shock waves is destroyed. Based on experimentation, such an approach was not found to be optimum because it did not allow for the precise introduction of fluid to the shock waves, which affects the output and particle size of the resulting aerosol burst. It should be noted that such an open design does have distinct advantages for thick, viscous fluids, because of the potential of clogging involved with the closed design, above first mentioned.
The preferred embodiment of the current invention draws liquid from a reservoir of medication that is preferably sufficient to hold 200 doses, and has been shown to produce reproducible doses of liquid medication. In the event that extremely precise dosing is desired, or if a change in dosing is desired from burst to burst, the current invention may be modified to consist of a small reservoir, or multiple small reservoirs, that contain the exact amount of liquid desired for delivery, and which is less than the nozzle will entrain with a given burst. Thus, the output of the inhaler is exactly equal to the contents of the reservoir, and may be easily changed from dose to dose.
Another approach that has been shown to be quite successful, is the use of blister packs pre-filled with the exact amount of liquid intended for aerosolization rather than the use of a reservoir. Prior to the contents of a blister cell being delivered, a feed tube, which is in fluid communication with the supersonic shock nozzle, is caused to puncture and penetrate the blister cell. Upon actuation of the nozzle, the contents of the blister cell is completely entrained into the shock nozzle and aerosolized. Blister packs also have the added advantage of better preserving medication than multiple dose reservoirs due to the limited exposure of the medication to air prior to aerosolization.
A complete discussion of the requirements for over, under, and perfectly expanded supersonic jets may be found in a text on compressible fluid dynamics. In general, the minimum pressure required to achieve supersonic flow in a nozzle is dependant upon the ambient discharge pressure and the supply pressure such that the ratio of the two should preferably be at least 0.5283 for air or oxygen and 0.5457 for carbon dioxide. Since all known inhalers have always discharged into roughly atmospheric conditions (14.7 psi), the resulting minimum supply pressure can be determined as being approximately equal to 27.8 psi or 13.1 psig for air or oxygen and 26.9 psi or 12.2 psig for carbon dioxide. In theory, these minimum supply pressures are sufficient to produce a flow of gas through the throat of a nozzle with a velocity equal to the speed of sound. In practice, higher pressures are required due to pressure losses and the expansion of gas into the internal volume of the device between the supply canister containing the stored gas and the choke of the nozzle. Although lower pressures above the calculated minimums will produce a degree of aerosolization, superior results are achieved with even higher pressures or continual increases in output for higher pressures. The increase in output for higher pressures is due to the increasing speed of the supersonic jet and the resulting increase in strength of the resulting shock waves. In the current embodiment of the invention, the pressure vessel is preferably filled with carbon dioxide to a pressure of approximately 750 psig, and the valve mechanism is designed to deliver a set amount of carbon dioxide with each actuation thereby controlling the repeatability of each dose and insuring that aerosol exiting the inhaler is produced primarily during the first few moments of contact between entrained liquid and the supersonic jet.
Supersonic jets produce shock waves in part because the jets don""t expand gradually to the diameter of the shock chamber. Due to the nature of the fluid dynamics involved, and conservation of momentum, supersonic jets expand by producing shock waves, thus producing an extreme change in pressure from one side of a shock wave to the other. Unlike other exiting flow patterns, supersonic jets, through the dynamics of the shock waves, maintain roughly the same diameter that the jets had as they exited from the nozzle from which the jets were produced. Similarly, vacuum and entrainment of liquid is not primarily due to the Bernoulli principle, but more to boundary layer friction between the exiting jet and the surrounding gas in the shock chamber.
Any nozzle (orifice) which supplies a compressed gas to the nozzle at pressures above the calculated minimums will have a supersonic jet exiting from it which is either over, under, or perfectly expanded, provided that there is nothing present to disturb the jet, such as a liquid. A nozzle may achieve a velocity greater than the speed of sound if it is supplied with sufficient supply pressure and has a gradually increasing cross-sectional area downstream of the throat or choke. The potential increase in velocity with increasing cross-sectional area is dependant on the total supply pressure. For the perfectly expanded supersonic jet, the cross-sectional area is increased to the maximum possible for the given supply pressure, resulting in a supersonic jet with a shock wave entirely enveloping the jet. Although this is ideal for the production of aerosol, it is impractical in practice because of variance in the supply pressure and the dimensional tolerances required.
An under expanded supersonic jet has a maximum cross-sectional area which is less than the perfectly expanded supersonic jet. The extreme example of an under expanded jet is a simple orifice with no increasing cross sectional area. The result of a under expanded supersonic jet is a series of expansion and compression reflected shock waves, with the first shock waves immediately after the exit of the jet being expansion waves.
An over expanded supersonic jet has a maximum cross sectional area which is greater than the maximum cross sectional area of the perfectly expanded supersonic jet. The result is also a series of reflected compression and expansion shock waves. In the preferred embodiment, an over expanded supersonic jet is instigated by placing a large radius on the exit edge of the nozzle. Upon the jet traveling through the jet and then subsequently along the radius, the initial response is for the jet to increase to a speed greater than the speed of sound followed by an over expansion of the jet, which will produce reflected shock waves. An over expanded supersonic jet has the slight advantage over an under expanded supersonic jet in that the first reflected shock waves emanating from the exit plane of the jet are compression waves and not expansion waves. In general, compression waves produce higher shear forces and thus would be expected to produce more aerosol and a smaller particle sizes.
Once the entrained liquid is aerosolized, the momentum of the jet carries the aerosol into a mouthpiece for immediate inhalation by the patient. Depending on the ability of the patient to coordinate actuation and inhalation, and the desired portion of the lung targeted for deposition, a spacer or valved holding chamber may be attached to the mouthpiece. Spacers and chambers allow for easier coordination of patient""s inhalation with device actuation, baffle out larger aerosol particles which are inappropriate for deposition within the lung, and allow more time for the liquid aerosol particles to evaporate, producing superior sized aerosol particles (1-3 microns) for deposition in the alveolar portions of the lung.
In accordance with another embodiment of the invention, a valve design is provided which is easier and less expensive to manufacture than in the previous embodiments. This embodiment includes a built in valved chamber for storing aerosol during inhalation, in contrast to the previous embodiments that allow for a chamber to be attached when desired. However, the invention is not limited to the use of a valved chamber or specific valve design.
The valved chamber stores aerosol upon actuation for subsequent inhalation in this embodiment. As is well known in the industry, and recently reported during in-vitro investigations (Respiratory Care, June 2000, Volume 45, Number 6, xe2x80x9cConsensus Conference on Aerosols and Delivery Devicesxe2x80x9d, page 628), valved chambers often maintain a static electric charge due to rinsing with water that causes a significant loss of aerosol particles due to mutual static electric attraction. This embodiment employs an anti-static plastic that prevents this phenomenon from occurring.
In addition to the properties described in the previous embodiments, the aerosolization process can be further optimized through placement of a liquid feed choke between the fluid reservoir containing the medication, and the liquid feeds that lead into the shock chamber. By further choking the flow of liquid down, it is possible to better control the introduction of fluid into the supersonic jet produced in the shock chamber, thus allowing for better aerosolization and an increase in the duration of the aerosol burst, although it is still a momentary phenomena relative to normal jet nebulization technologies.
Additionally, the shock wave aerosolization process functions remarkably well with micronized powder in blister packs as well. Blister packs, containing one or more cells, are used to store a pre-determined amount of liquid or powder. Prior to aerosolization, a feed tube, which is in fluid communication with the shock wave aerosolization process nozzle, is inserted into the blister pack cell. Subsequent to the insertion of the feed tube, the carbon dioxide valve is actuated, creating a set burst of gas. As previously described, the carbon dioxide exits the throat of the jet, causing a vacuum, which entrains the micronized powder or liquid through the feed tube and into the shock chamber. As previously described with liquid medication, when medicinal powder is entrained it becomes efficiently aerosolized in the reflected shock waves and carried out to the mouthpiece or valve chamber, as intended.
An object of the invention is to provide an inhaler, which can deliver a repeatable dose of aerosol containing particles appropriately sized for deposition within the patient""s lung.
Another object of the invention is to provide an inhaler, which can produce aerosol particles appropriate for deposition in the bronchial airways.
Another object of the invention is to provide an inhaler, which can produce aerosol particles appropriate for deposition in the alveolar portions of the lung.
Another object of the invention is to provide an inhaler, which can aerosolize an aqueous solution.
Another object of the invention is to provide an inhaler, which can aerosolize a suspension of medication in liquid.
Another object of the invention is to provide an inhaler, which can aerosolize liquid pharmaceutical formulations currently available only for nebulizers.
Another object of the invention is to provide an inhaler, which does not mix medication and propellant prior to aerosolization.
Another object of the invention is to provide an inhaler, which can deliver combinations of different medications with one burst.
Another object of the invention is to provide an inhaler with an acceptable aftertaste.
Another object of the invention is to provide an inhaler, which is portable, convenient and easy to use.
Another object of the invention is to provide an inhaler, which is inexpensive to produce.
Another object of the invention is to provide an inhaler that has a built in valved chamber for storage of aerosol.
Another object of the invention is to provide an invention that works in conjunction with blister packs that contain either liquid or powder.
Further objects and advantages of the invention will be brought out in the following portions of the specification, wherein, the detailed description is for the purpose of fully disclosing preferred embodiments of the invention without placing limitations thereon.